CICI IRMA ARIFIN

1111012073
KELAS A
The four types of testing proe!ures th"t
re#uire $"%i!"tion &hen testing st"rting
'"teri"%s for use in o'p%e'ent"ry
'e!iines "re(

)u"ntit"ti$e tests for(

* the "ti$e su+st"ne,
* the "epte! ther"peuti"%%y "ti$e
o'ponent-s. or
'"r/er-s.1 in " #u"nti0e! her+"%
su+st"ne1 or
* i'purities in the su+st"ne2

Li'it tests for the ontro% of i'purities in

the su+st"ne2

I!enti0"tion tests for the su+st"ne2

Chro'"togr"phi pro0%ing -0ngerprinting.

of " her+"% st"rting '"teri"%2

Validation of quantitative tests of

content
Any st"n!"r!s use! in $"%i!"tion or
su+se#uent testing 'ust +e "+%e to +e tr"e!
+"/ to "n "uthenti"te! pri'"ry st"n!"r!2 If
no ph"r'"opoei"% st"n!"r! is "$"i%"+%e, or
seon!"ry st"n!"r! !eri$e! thereof, the
suit"+i%ity of the "uthenti"tion proess 'ust
+e on0r'e!2

Validation of limit tests

Li'it tests "re use! to ontro% either the
"'ounts of gener"% i'purities -for e3"'p%e,
"sh,
'oisture, et2. in the su+st"ne or the
"'ounts of " spei0 o'ponent -for
e3"'p%e, resi!u"% st"rting '"teri"%s in the
su+st"ne or !egr"!"tion pro!uts.2

Validation of identifcation tests (other

than profling tests)
A %"/ of spei0ity in one "n"%yti"%
proe!ure ou%! +e o'pens"te! +y other
supporting "n"%yti"% proe!ures2 Any
st"n!"r!s use! in $"%i!"tion or su+se#uent
testing 'ust +e "+%e to +e tr"e! +"/ to "n
"uthenti"te! pri'"ry st"n!"r!2

Validation of chromatographic profling

(fngerprinting) tests
Co'p%e3 o'p%e'ent"ry st"rting '"teri"%s
"n so'eti'es +e i!enti0e! using "
hro'"togr"phi pro0%ing proe!ure for the
su+st"ne2
The hro'"togr"phi pro0%ing 'etho! "n +e
soure! fro' " ph"r'"opoei", " peer
re$ie&e! 'onogr"ph or pu+%i"tion or it "n
+e "$"i%"+%e "s " propriet"ry 'etho!2 Any
st"n!"r!s use! in $"%i!"tion or su+se#uent
testing 'ust +e "+%e to +e tr"e! +"/ to "n
"uthenti"te! pri'"ry st"n!"r!2
STARTIN4 MATERIALS F5R MAN6FACT6RIN4 5F
78ARMACE6TICALS M6ST C5M7L9 :IT8
INTERNATI5NAL STAN;AR;S
As ont"'in"tion is 'ost %i/e%y to our
either !uring '"nuf"ture of the st"rting
'"teri"% itse%f or !uring its tr"!ing,
tr"nsport"tion "n! !istri+ution to the
ph"r'"euti"% '"nuf"turer of the 0n"%
!rug pro!ut, the group<s '"=or
reo''en!"tions "!!resse! these "re"s2

M"nuf"turing "ti$ities &ith st"rting

'"teri"%s for ph"r'"euti"% pro!uts
shou%! +e o$ere! +y "n "uthori>"tion, fro'
the o'petent he"%th "uthority, re#uiring
"!herene to 4oo! M"nuf"turing 7r"tie
-4M7.2 4o$ern'ent"% inspetor"tes shou%!
"%so +e "+%e to on!ut inspetions of
'"nuf"turing f"i%ities "t "ny ti'e "n!
p%"e "n! +e "+%e to inspet ont"iners of
st"rting '"teri"% pro!ue!2
It &"s reo''en!e! th"t :85 itse%f
shou%! "ti$e%y !e$e%op " %ist of riti"%
e3ipients -in"ti$e st"rting '"teri"%s. "n!
their no'en%"ture2 This &ou%! "i!
'"nuf"turers, tr"!ers, inspetor"tes "n!
other o?i"%s in reogni>ing "n! he/ing
the #u"%ity of st"rting '"teri"%s for
ph"r'"euti"% pro!uts2

Further'ore, the group reo''en!e! th"t e"h

'"nuf"turer or ountry shou%! h"$e testing
f"i%ities for "n"%ysis of st"rting '"teri"%s "n! 0n"%
ph"r'"euti"% pro!uts2 :here no suh "n"%ysis
is possi+%e, :85 shou%! "%so "!$ise !e$e%oping
ountries to use for'u%"tions in essenti"% !rugs
&ith ingre!ients for &hih they h"$e "ppropri"te
testing f"i%ities2 :here"s e$ery p"rty in the h"in
h"s his o&n responsi+i%ities, the 0n"% responsi+i%ity
re'"ins &ith the '"nuf"turer of the 0n"%
pro!ut2

F;A<s Guidance for Submitting Supporting

Documentation in Drug Applications for the
Manufacture of Drug Substances note!
th"t &h"t onstitutes " st"rting '"teri"%
'"y not "%&"ys +e o+$ious2
The fo%%o&ing riteri" '"y +e he%pfu%(

It is inorpor"te! into the ne& !rug

su+st"ne "s "n i'port"nt strutur"%
e%e'ent

It is o''eri"%%y "$"i%"+%e

It is " o'poun! &hose n"'e, he'i"%

struture, he'i"% "n! physi"%
h"r"teristis "n! properties, "n!
i'purity pro0%e "re &e%% !e0ne! in the
he'i"% %iter"ture

It is o+t"ine! +y o''on%y /no&n

proe!ures -this "pp%ies prinip"%%y to
st"rting '"teri"%s e3tr"te! fro' p%"nts
"n! "ni'"%s, "n! to se'i*syntheti
"nti+iotis.2
Se%etion of st"rting '"teri"%s

Design space.
The tr"!ition"% "ppro"h to st"rting '"teri"%
i!enti0"tion "n! !e$e%op'ent h"s in$o%$e!
on%y t&o steps(

7ro$i!e 'ini'"% st"rting '"teri"%

infor'"tion "+out the %e$e% "n! f"te of
i'purities

;e0ne "n! '"int"in tight spei0"tions

for st"rting '"teri"% "n! !rug su+st"nes
to o'pens"te for %i'ite! syntheti
/no&%e!ge2
In ontr"st, the !esign sp"e "ppro"h
in$o%$es the fo%%o&ing(

Se%et st"rting '"teri"%s +"se! on

sienti0 un!erst"n!ing of the !rug
su+st"ne synthesis "n! "$"i%"+%e ontro%
'eh"nis's

6n!erst"n! the soure, for'"tion, "n! f"te

of i'purities

6n!erst"n! ho& h"nges to the synthesis

of the st"rting '"teri"% '"y in@uene
i'purity pro0%es2

Process control

Analytical control.
At the he"rt of " strong =usti0"tion for "
st"rting '"teri"% is the !e'onstr"tion of
"!e#u"te "n"%yti"% ontro% of the registere!
proess2 This &i%% in%u!e !"t" "+out(

The initi"% h"r"teri>"tion of the

st"rting '"teri"%, in%u!ing "n o$er$ie&
of st"+i%ity of the iso%"te! st"rting
'"teri"%

St"rting '"teri"% +"th !"t" fro'

$"rious supp%iers use! !uring
!e$e%op'ent

An "ssess'ent of ho& proess h"nges

ou%! "Aet i'purity pro0%es

;e'onstr"tion of the se%eti$ity of "n

"n"%yti"% 'etho! for /no&n "n!
potenti"% i'purities2

Change control.
;e'onstr"tion of " ro+ust h"nge ontro%
syste' o$ering +oth the sponsor<s "ti$ities
"n! those of its supp%iers pro$i!es "ssur"ne
th"t future inno$"tion &i%% not un!er'ine
p"tient s"fety2 In*house h"nge ontro%
progr"'s "n! $en!or "ssur"ne progr"'s "re
" $it"% p"rt of the o$er"%% ontro% of !rug
su+st"ne #u"%ity2 The h"nge ontro%
'eh"nis' shou%! "ssess potenti"% h"nges
for their in@uene on riti"% #u"%ity "ttri+utes
of the !rug su+st"ne2
Con%usion
To ensure p"tient s"fety "n! o+t"in
regu%"tory "ppro$"%, " st"rting '"teri"% for
" !rug su+st"ne synthesis 'ust +e
=usti0e! "g"inst " set of pre!e0ne! riteri"
"s out%ine! +y $"rious regu%"tory
"uthorities2 6sing " siene* "n! ris/*+"se!
"ppro"h, the "uthors propose th"t " g%o+"%
regu%"tory str"tegy to =ustify st"rting
'"teri"%s "n +e +"se! on the ontro% of
three /ey the'es, n"'e%y(

7roess ontro%

An"%yti"% ontro%

Ch"nge ontro%2